Angiotensin converting enzyme (ACE) mainly presents in human vascular endothelial cells, lungs, kidneys and brains. This enzyme may convert inactive angiotensin I to active angiotensin II by cleaving two amino acids (His-Leu) from the C-terminus end so as to cause contraction of blood vessels and increase blood pressure. Meanwhile, ACE may inactivate the bradykinin that exhibits the function of relief of blood vessels. Thus, ACE may increase blood pressure.
The binding of Angiotensin converting enzyme inhibitor (ACEI) to ACE may reduce the formation of angiotensin II and the inactivation of bradykinin. If ACEI is added to foods, it will cause positive effect on decreasing hypertensive symptom. For the present, it is known that many peptides have the effect on the inhibition of ACE. They have different amino acid sequences and lengths. Those peptides having ACE inhibitory activity can be isolated from foods. Those foods include the hydrolysates of animal or plant proteins, such as casein (Maruyama and Suzuki, 1982), corn protein (Miyoshi et al., 1991), sardine meat (Matsui et al., 1993) and bonito (Matsumura et al., 1993); and fermented foods, such as sake and wine residue (Saito et al., 1994), soy bean oil (Kinoshita et al., 1993), cheese (Okamoto et al., 1995) and fermented milk (Nakamura et al., 1995) etc.
Japanese Patent No. 5-87052 and Japanese Laid-Open Patent Publication No. 2-154693 disclose the substances containing oligopeptides. Food Chemical Monthly, 1990, 6:80 also discloses specific oligopeptides which have the improved effect on lipid metabolism, including the reduction of the concentration of triglyceride in blood. These substances containing oligopeptides described in the above patents or references are the mixtures of protein hydrolysates. However, they do no describe the amino acid sequences of the active ingredients of mixtures. The purity of the above-mentioned substances containing peptides is relatively low and can not be used as pharmaceuticals. Further, when those substances are contained in foods, they are very difficult to be quantitatively detected from other peptides contained in foods. This would cause some problems in quality control.
Japanese Laid-Open Patent Publication No. 6-298794 discloses a process for the preparation of ACEI from the proteins of animal and plant sources, such as fish meats, pork and chicken. The process utilizes protein hydrolase, such as thermolysin, pepsin or trypsin, in suitable medium and under proper conditions to decompose the starting materials. The hydrolysate is subject to centrifugation, filtration, concentration and resin absorption to obtain the peptides with ACE inhibitory activity. Japanese Laid-Open Patent Publication No. 5-331192 discloses the hydrolysis of katsubushi by thermolysin to produce the peptides with ACE inhibitory activity. The sequence of the peptide is H-Tyr-Ser-Trp-Ala-OH. Japanese Laid-Open Patent Publication No. 4-264098 discloses the preparation of the peptides with ACE inhibitory activity from chicken meats containing no fat. The sequence of the peptide is Gln-Lyn-Pro-Lys-Arg. U.S. Pat. No. 5,854,029 discloses a process for the preparation of the dipeptide Tyr-Pro exhibiting ACE inhibitory activity. In the process, lactobacillus is incubated in the peptide and/or protein medium containing Tyr-Pro to obtain an incubation solution containing a large amount of Tyr-Pro.
Among the above-mentioned prior art techniques, most of them utilize different hydrolase, separation and purification method from animal proteins, such as fish meat, chicken or pork to prepare the peptides with ACE inhibitory activity. However, the cost of the starting materials is more expensive.